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Title: Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

Abstract

Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as ~58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species–species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution ismore » reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species–species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15–protein engagements was illuminated.« less

Authors:
; ; ; ; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIAID
OSTI Identifier:
1506505
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section D. Structural Biology
Additional Journal Information:
Journal Volume: 75; Journal Issue: 1; Journal ID: ISSN 2059-7983
Publisher:
IUCr
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Langley, Caroline, Goodwin, Octavia, Dzimianski, John V., Daczkowski, Courtney M., and Pegan, Scott D. Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement. United States: N. p., 2019. Web. doi:10.1107/S2059798318015322.
Langley, Caroline, Goodwin, Octavia, Dzimianski, John V., Daczkowski, Courtney M., & Pegan, Scott D. Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement. United States. doi:10.1107/S2059798318015322.
Langley, Caroline, Goodwin, Octavia, Dzimianski, John V., Daczkowski, Courtney M., and Pegan, Scott D. Tue . "Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement". United States. doi:10.1107/S2059798318015322.
@article{osti_1506505,
title = {Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement},
author = {Langley, Caroline and Goodwin, Octavia and Dzimianski, John V. and Daczkowski, Courtney M. and Pegan, Scott D.},
abstractNote = {Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as ~58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species–species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution is reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species–species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15–protein engagements was illuminated.},
doi = {10.1107/S2059798318015322},
journal = {Acta Crystallographica. Section D. Structural Biology},
issn = {2059-7983},
number = 1,
volume = 75,
place = {United States},
year = {2019},
month = {1}
}